DESCRIPTION(adapted from applicant's abstract): Acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID), is widely used for treatment of pain and/or fever in the elderly. This dual action is sometimes contraindicated. In many instances pain needs to be controlled without masking the symptomatic fever (e.g., postoperative period). Acetaminophen can also cause hepatotoxicity, particularly after ingestion of large doses or chronic use of smaller doses (especially in the elderly or when liver function is affected) that can lead to death. Therefore, there is a need for new more selective compounds with greater pharmacological potency and devoid of hepatotoxic or antipyretic effect. We are exploring a series of new proprietary derivatives of acetaminophen. In preliminary studies, one of these compounds (SCP-1) demonstrated high analgesic activity free from antipyretic activity and hepatotoxicity. In this STTR project we propose to further characterize SCP-1 and compare biological properties with acetaminophen. We will also explore combinations of SCP-1 with morphine (and with other pain relievers) to confirm preliminary studies indicating a synergistic effect of this combination. The Phase I experiments will help us ascertain the legitimacy of SCP-1 as a lead candidate drug worthy of further development and testing in Phase II for the treatment of chronic and post-operative pain in the elderly. PROPOSED COMMERCIAL APPLICATION: The market for pain relievers in the US is estimated to be $4 billion annually. Acetaminophen (marketed under the name Tylenol(TM) and other brand names) represents about 40% of that market. Although widely used, acetaminophen is not without some serious side effects. There is a clear unmet medical need for pain relievers that are effective but have a better safety profile than acetaminophen. The research proposed in this grant application is directed at developing a pain reliever that is as effective as acetaminophen but with fewer side effects. This drug would be targeted at those patients most at risk from acetaminophen toxicity, the elderly, particularly those who must take pain relievers on a chronic basis, and those experiencing post-operative pin where masking the symptomatic fever could delay the diagnosis of infection.